Periodontitis and type 2 diabetes: is oxidative stress the mechanistic link?
Periodontitis is a common, chronic inflammatory disease initiated by bacteria which has an increased prevalence and severity in patients with type 2 diabetes. Recent studies indicate that the co-morbid presence of periodontitis can, in turn, adversely affect diabetic status and the treatment of periodontitis can lead to improved metabolic control in diabetes patients. Current evidence points to a bidirectional interrelationship between diabetes and inflammatory periodontitis. The importance of oxidative stress-inflammatory pathways in the pathogenesis of type 2 diabetes and periodontitis has recently received attention. Given the bidirectional relationship between these two conditions, this review discusses the potential synergistic interactions along the oxidative stress-inflammation axis common to both type 2 diabetes and periodontitis, and the implications of this relationship for diabetic patients.


Models of symbiosis.
A tentative outline of concepts is proposed for the evolutionary genetics of symbiosis. There are three main topics. The first concerns the tension between the integrative and disruptive forces of kin selection. Kin selection can be disruptive because competition among close relatives favors dispersal and a reduction in relatedness among neighbors. Kin selection acts independently within each species of a symbiotic community but has important consequences for the integration of the community into a cooperative unit. The second topic describes the evolution of beneficial, synergistic effects between species. The evolution of mutual effects depends on various correlations between species. Genetic correlations are analogous to linkage disequilibrium in standard Mendelian genetics. Correlations in reproductive success between symbiotic partners arise from codispersal and reproductive synchrony. The third topic concerns the evolution of asymmetrical symbioses in which one species can dominate its partner. Dominance may explain the evolution of uniparental inheritance among cytoplasmic symbionts and a peculiar form of germ-soma separation in the symbionts of insects.


The influence of spleen size on liver regeneration after major hepatectomy in normal and early cirrhotic liver.
The relationship between liver regeneration and spleen size after major hepatectomy in normal and cirrhotic liver was studied by single photon emission computed tomography (SPECT). Twenty-six patients, 18 patients with normal liver and eight patients with cirrhotic liver, receiving major hepatectomy were included. Liver and spleen volumes were measured by SPECT before major hepatectomy, 6 months, 1 year and 2 years after operation. The correlation of liver and spleen volume during liver regeneration was analyzed. In both groups, the residual liver volume increased within the first year and decreased in the second year. No difference in regeneration ability was found. The spleen volume in cirrhotic liver was increased, with a trend similar to normal liver during the first year. In contrast, the increased spleen volume persisted up to the second year in cirrhotic patients. Age per year, the female sex, and body surface index had a positive correlation with increased percentage of liver volume. The spleen volume per 100 ml with time played a significantly negative role in increasing percentage of liver volume, confidence interval: -2.16 to -27.92, P=0.011. In early cirrhotic liver within normal functional limits, the liver still could regenerate as a normal liver after major hepatectomy in 1 year. Age, the female sex, and body surface index had positive correlation but the size of spleen volume played a negative role to regenerative liver volume.


The Syk protein tyrosine kinase is essential for Fcgamma receptor signaling in macrophages and neutrophils.
The cytoplasmic protein tyrosine kinase Syk has two amino-terminal SH2 domains that engage phosphorylated immunoreceptor tyrosine-based activation motifs in the signaling subunits of immunoreceptors. Syk, in conjunction with Src family kinases, has been implicated in immunoreceptor signaling in both lymphoid and myeloid cells. We have investigated the role of Syk in Fcgamma receptor (FcgammaR)-dependent and -independent responses in bone marrow-derived macrophages and neutrophils by using mouse radiation chimeras reconstituted with fetal liver cells from Syk-/- embryos. Chimeric mice developed an abdominal hemorrhage starting 2 to 3 months after transplantation that was ultimately lethal. Syk-deficient neutrophils derived from the bone marrow were incapable of generating reactive oxygen intermediates in response to FcgammaR engagement but responded normally to tetradecanoyl phorbol acetate stimulation. Syk-deficient macrophages were defective in phagocytosis induced by FcgammaR but showed normal phagocytosis in response to complement. The tyrosine phosphorylation of multiple cellular polypeptides, including the FcgammaR gamma chain, as well as Erk2 activation, was compromised in Syk-/- macrophages after FcgammaR stimulation. In contrast, the induction of nitric oxide synthase in macrophages stimulated with lipopolysaccharide and gamma interferon was not dependent on Syk. Surprisingly, Syk-deficient macrophages were impaired in the ability to survive or proliferate on plastic petri dishes. Taken together, these results suggest that Syk has specific physiological roles in signaling from FcgammaRs in neutrophils and macrophages and raise the possibility that in vivo, Syk is involved in signaling events other than those mediated by immunoreceptors.


Deleted in breast cancer 1 limits adipose tissue fat accumulation and plays a key role in the development of metabolic syndrome phenotype.
Obesity is often regarded as the primary cause of metabolic syndrome. However, many lines of evidence suggest that obesity may develop as a protective mechanism against tissue damage during caloric surplus and that it is only when the maximum fat accumulation capacity is reached and fatty acid spillover occurs into to peripheral tissues that metabolic diseases develop. In this regard, identifying the molecular mechanisms that modulate adipocyte fat accumulation and fatty acid spillover is imperative. Here we identify the deleted in breast cancer 1 (DBC1) protein as a key regulator of fat storage capacity of adipocytes. We found that knockout (KO) of DBC1 facilitated fat cell differentiation and lipid accumulation and increased fat storage capacity of adipocytes in vitro and in vivo. This effect resulted in a "healthy obesity" phenotype. DBC1 KO mice fed a high-fat diet, although obese, remained insulin sensitive, had lower free fatty acid in plasma, were protected against atherosclerosis and liver steatosis, and lived longer. We propose that DBC1 is part of the molecular machinery that regulates fat storage capacity in adipocytes and participates in the "turn-off" switch that limits adipocyte fat accumulation and leads to fat spillover into peripheral tissues, leading to the deleterious effects of caloric surplus.


Spatiotemporally photoradiation-controlled intratumoral depot for combination of brachytherapy and photodynamic therapy for solid tumor.
In an attempt to spatiotemporally control both tumor retention and the coverage of anticancer agents, we developed a photoradiation-controlled intratumoral depot (PRCITD) driven by convection enhanced delivery (CED). This intratumoral depot consists of recombinant elastin-like polypeptide (ELP) containing periodic cysteine residues and is conjugated with a photosensitizer, chlorin-e6 (Ce6) at the N-terminus of the ELP. We hypothesized that this cysteine-containing ELP (cELP) can be readily crosslinked through disulfide bonds upon exposure to oxidative agents, specifically the singlet oxygen produced during photodynamic stimulation. Upon intratumoral injection, CED drives the distribution of the soluble polypeptide freely throughout the tumor interstitium. Formation and retention of the depot was monitored using fluorescence molecular tomography imaging. When imaging shows that the polypeptide has distributed throughout the entire tumor, 660-nm light is applied externally at the tumor site. This photo-radiation wavelength excites Ce6 and generates reactive oxygen species (ROS) in the presence of oxygen. The ROS induce in situ disulfide crosslinking of the cysteine thiols, stabilizing the ELP biopolymer into a stable therapeutic depot. Our results demonstrate that this ELP design effectively forms a hydrogel both in vitro and in vivo. These depots exhibit high stability in subcutaneous tumor xenografts in nude mice and significantly improved intratumoral retention compared to controls without crosslinking, as seen by fluorescent imaging and iodine-125 radiotracer studies. The photodynamic therapy provided by the PRCITD was found to cause significant tumor inhibition in a Ce6 dose dependent manner. Additionally, the combination of PDT and intratumoral radionuclide therapy co-delivered by PRCITD provided a greater antitumor effect than either monotherapy alone. These results suggest that the PRCITD could provide a stable platform for delivering synergistic, anti-cancer drug depots.


Intranuclear distribution of Epstein-Barr virus-encoded nuclear antigens EBNA-1, -2, -3 and -5.
Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs) express at least seven virally encoded proteins. Their functional role, and their relationships to each other and to normal nuclear constituents are virtually unknown. As the first step towards a topographical study, the intranuclear distribution of EBV-encoded nuclear antigens EBNA-1, -2, -3 and -5 (abbreviated E1, E2 etc.) was examined in EBV-transformed LCLs by immunofluorescence and digital image analysis of fluorescence patterns. E1-E3 showed a finely granular distribution. The E2 patterns were virtually identical when comparing indirect staining using an E2-specific mouse monoclonal antibody with anticomplement immunofluorescence using a human antibody, rendered monospecific to E2 by absorption. The E1/E2 patterns showed 32% overlap and the E2/E3 10% overlap in the high overlap category (66.7-100%), while the E2/E2 comparison with two reagents showed 61% overlap in this category. This suggests that E2 and E3 largely appear in different nuclear structures, whereas E1 appears to be randomly distributed with regard to E2. The E5 pattern was radically different from that of E1, E2 and E3. The anti-E5 mouse monoclonal antibody detected 4-10 huge, globular, sharply circumscribed dots, located in dispersed chromatin areas, while the distribution of E1, E2 and E3 showed no obvious relationship to chromatin distribution. The methods described here allow a more refined topographical analysis of the EBNA protein family, mostly in relation to each other, in relation to other nuclear proteins, and with respect to specialized functional domains in interphase chromatin.(ABSTRACT TRUNCATED AT 250 WORDS)


Characterization of stabilized/solidified refinery oily sludge and incinerated refinery sludge with cement using XRD, SEM and EXAFS.
Solidification/stabilization (S/S) of refinery oily sludge and incinerated oily sludge (ash) with cement type I42.5 and II42.5 was investigated using, X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) combined with Energy Dispersive Spectroscopy (EDS) and Extended X-ray Absorption Fine Structure (EXAFS). The results showed that delayed ettringite formation (DEF) and major cement hydration reactions occurred. XRD analysis of S/S oily sludge samples revealed cement-bearing solid phases, such as portlandite, calcite, C(3)S, C(2)S and C(4)AF. SEM analysis, confirmed ettringite at solidified oily sludge samples. Solidified ash samples contained ettringite substituted by chromates. However, solid phases found in solidified ash samples with I42.5 cement showed minor variation in type and structure compared to those observed in solidified ash samples with II42.5 cement. Fe K edge EXAFS analysis revealed the presence of iron oxides in both S/S wastes. The comparison between spectra of the S/S resulting materials and the ones of their original components, showed that the first sphere Fe-O distances were longer than in the pure iron oxide thereby providing evidence that the resulting materials were not simple mixtures, but products of a reaction that modified the local environment of iron.


Detection of mines and minelike targets using principal component and neural-network methods.
This paper introduces a new system for real-time detection and classification of arbitrarily scattered surface-laid mines from multispectral imagery data of a minefield. The system consists of six channels which use various neural-network structures for feature extraction, detection, and classification of targets in six different optical bands ranging from near UV to near IR. A single-layer autoassociative network trained using the recursive least square (RLS) learning rule was employed in each channel to perform feature extraction. Based upon the extracted features, two different neural-network architectures were used and their performance was compared against the standard maximum likelihood (ML) classification scheme. The outputs of the detector/classifier network in all the channels were fused together in a final decision-making system. Two different final decision making schemes using the majority voting and weighted combination based on consensual theory were considered. Simulations were performed on real data for six bands and on several images in order to account for the variations in size, shape, and contrast of the targets and also the signal-to-clutter ratio. The overall results showed the promise of the proposed system for detection and classification of mines and minelike tagets.


Localization of mutant ubiquitin in the brain of a transgenic mouse line with proteasomal inhibition and its validation at specific sites in Alzheimer's disease.
Loss of protein quality control by the ubiquitin-proteasome system (UPS) during aging is one of the processes putatively contributing to cellular stress and Alzheimer's disease (AD) pathogenesis. Recently, pooled Genome Wide Association Studies (GWAS), pathway analysis and proteomics identified protein ubiquitination as one of the key modulators of AD. Mutations in ubiquitin B mRNA that result in UBB(+1) dose-dependently cause an impaired UPS, subsequent accumulation of UBB(+1) and most probably depositions of other aberrant proteins present in plaques and neurofibrillary tangles. We used specific immunohistochemical probes for a comprehensive topographic mapping of the UBB(+1) distribution in the brains of transgenic mouse line 3413 overexpressing UBB(+1). We also mapped the expression of UBB(+1) in brain areas of AD patients selected based upon the distribution of UBB(+1) in line 3413. Therefore, we focused on the olfactory bulb, basal ganglia, nucleus basalis of Meynert, inferior colliculus and raphe nuclei. UBB(+1) distribution was compared with established probes for pre-tangles and tangles and Aβ plaques. UBB(+1) distribution found in line 3413 is partly mirrored in the AD brain. Specifically, nuclei with substantial accumulations of tangle-bearing neurons, such as the nucleus basalis of Meynert and raphe nuclei also present high densities of UBB(+1) positive tangles. Line 3413 is useful for studying the contribution of proteasomal dysfunction in AD. The findings are consistent with evidence that areas outside the forebrain are also affected in AD. Line 3413 may also be predictive for other conformational diseases, including related tauopathies and polyglutamine diseases, in which UBB(+1) accumulates in their cellular hallmarks.


A human model for study of blood-vascular wall interactions. Effects of enzymatic treatment of intima.
A human umbilical cord vein model was used to study the interaction of human blood with vein intima after treatment with certain enzymes. Treatment of the intima with neuraminidase produced little in the way of morphologic change, and studies showed no increase in the retention of platelets labeled with chromium 51. Treatment of vein intima with collagenase produced severe morphologic changes, with exposure of coarse and fine subendothelial fibers, but with the retention of platelets little enhanced, as determined morphologically or radiometrically. On the other hand, treatment of vein intima with trypsin resulted in loss of endothelium in some areas, with exposure of coarse subendothelial fibers that produced a marked increase in platelet retention, as determined both morphologically and radiometrically. Exposure of the vein intima to thrombin produced apparent contraction of endothelial cells, with focal exposure of subendothelium and platelet adhesion.


[Morphogenetic role of the cortex in the development of twins in sea urchins].
The dynamics of development of Strongylocentrotus nudus sea urchin twins has been studied after centrifugation at 2,000 g for 5 min and incubation in hypotonic medium after fertilization till formation of the first cleavage furrow. Cortex rigidity was found to correlate with the frequency of twins occurrence. The largest amount of twins forms after centrifugation and hypotonic treatment for the first 1-6 min of zygote development. The twins may be obtained at 25-40 min of development by centrifugation in the presence of cytochalasin B (1 micrograms/ml). Morphogenetic role of cortex in development of sea urchin twins has been discussed.


MicroRNA expression and identification of putative miRNA targets in ovarian cancer.
MicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Emerging evidence suggests the potential involvement of altered regulation of miRNA in the pathogenesis of cancers, and these genes are thought to function as both tumor suppressors and oncogenes. Using microRNA microarrays, we identify several miRNAs aberrantly expressed in human ovarian cancer tissues and cell lines. miR-221 stands out as a highly elevated miRNA in ovarian cancer, while miR-21 and several members of the let-7 family are found downregulated. Public databases were used to reveal potential targets for the highly differentially expressed miRNAs. In order to experimentally identify transcripts whose stability may be affected by the differentially expressed miRNAs, we transfected precursor miRNAs into human cancer cell lines and used oligonucleotide microarrays to examine changes in the mRNA levels. Interestingly, there was little overlap between the predicted and the experimental targets or pathways, or between experimental targets/pathways obtained using different cell lines, highlighting the complexity of miRNA target selection. Our results identify several differentially expressed miRNAs in ovarian cancer and identify potential target transcripts that may be regulated by these miRNAs. These miRNAs and their targets may have important roles in the initiation and development of ovarian cancer.


Emerging foodborne diseases.
The epidemiology of foodborne diseases is rapidly changing. Recently described pathogens, such as Escherichia coli O157:H7 and the epidemic strain of Salmonella serotype Typhimurium Definitive Type 104 (which is resistant to at least five antimicrobial drugs), have become important public health problems. Well-recognized pathogens, such as Salmonella serotype Enteritidis, have increased in prevalence or become associated with new vehicles. Emergence in foodborne diseases is driven by the same forces as emergence in other infectious diseases: changes in demographic characteristics, human behavior, industry, and technology; the shift toward a global economy; microbial adaptation; and the breakdown in the public health infrastructure. Addressing emerging foodborne diseases will require more sensitive and rapid surveillance, enhanced methods of laboratory identification and subtyping, and effective prevention and control.


Posttraumatic stress symptoms in mothers of premature infants.
To examine mothers' responses to having a premature infant in the neonatal intensive-care unit and to determine the degree to which they appear similar to a posttraumatic stress response. Mothers were enrolled in this descriptive, correlational study shortly before the infant was discharged from the hospital. Data were collected at enrollment and when the infant was 6 months old, corrected for prematurity. A convenience sample of 30 mothers of high-risk premature infants. None. A semistructured interview of the mothers was conducted at 6 months corrected age. Interview responses were analyzed to identify three symptoms related to posttraumatic stress disorder: re-experiencing, avoidance, and increased arousal. Other measures focused on maternal psychological well-being--neonatal intensive-care unit stress, depressive symptoms, and worry about the infant--and demographic characteristics. Infant illness severity included birth weight, length of mechanical ventilation, multiple birth, and the severity of neurological insults. All mothers interviewed had at least one posttraumatic symptom, 12 had two, and 16 had three symptoms. Twenty-six mothers reported increased arousal; re-experiencing and avoidance were reported by 24 mothers each. The number, but not the type, of posttraumatic stress symptoms was related to maternal psychological well-being. Maternal demographic characteristics, except marital status, and infant illness severity, were unrelated to posttraumatic stress symptoms. These mothers appeared to be experiencing emotional responses similar to posttraumatic stress reactions at 6 months after their child's expected birth date. Since maternal emotional responses may affect the parenting of premature infants, additional nursing research is needed provide a basis for interventions with these highly vulnerable mothers and infants.


Evaluating contemporary radiotherapy approaches in the primary treatment of cervical cancer.
Radiotherapy with concurrent cisplatinum-based chemotherapy became a standard recommendation for the management of advanced cervical cancer in 1999. We reviewed our experience with this approach to determine the impact on patient outcomes. A retrospective review of all cervical cancer patients treated with curative intent using radical radiotherapy +/- chemotherapy from 1992 to 2005 was performed. Survival and relapse rates were analyzed using the Kaplan-Meier method and were compared using the log-rank test. During this period, 224 treated patients were identified: 153 (68%) were treated between 1992 and 1999 (group 1) and 71 (32%) were treated after 1999 (group 2). The median age was 53 and 55 years with a median follow-up of 49 and 34 months for groups 1 and 2, respectively. Stage classification and histological diagnosis were similar for both groups. Treatment usually consisted of external beam pelvic radiotherapy (40-45 Gy in 20-25 fractions) followed by low-dose rate brachytherapy (35-40 Gy to point A). Chemotherapy consisted of weekly intravenous cisplatinum (40 mg/m2) given concurrently with pelvic radiation. The proportion of patients receiving chemotherapy increased significantly after 1999, 12% in group 1 compared with 79% in group 2 (P < 0.01). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 53% and 54% for group 1 and 64% and 67% for group 2. The improvement in PFS for group 2 approached statistical significance (P = 0.06), but the difference in OS did not. There has been a significant increase in the use of concurrent chemoradiation for cervical cancer treatment after 1999, and this seems to have led to higher rates of PFS and OS, although these have yet to achieve statistical significance.


The causal link between self-reported trauma and dissociation: a critical review.
The idea that traumatic experiences cause dissociative symptoms is a recurrent theme in clinical literature. The present article summarizes evidence that cast doubts on the commonly voiced view that the connection between self-reported trauma and dissociation is a simple and robust one. It is argued that: (1) the correlations between self-reported traumatic experiences and dissociative symptoms reported in the literature are, at best, modest; (2) other factors may act as a third variable in the relationship between trauma and dissociation; and (3) high scores on the Dissociative Experiences Scale are accompanied by fantasy proneness, heightened suggestibility, and susceptibility to pseudomemories. These correlates of dissociation may promote a positive response bias to retrospective self-report instruments of traumatic experiences. Thus, the possibility that dissociation encourages self-reported traumatic experiences rather than vice versa merits investigation. While attractive, simple models in which trauma directly causes dissociation are unlikely to be true.


Charge optimized many body (COMB) potentials for Pt and Au.
Interatomic potentials for Pt and Au are developed within the third generation charge optimized many-body (COMB3) formalism. The potentials are capable of reproducing phase order, lattice constants, and elastic constants of Pt and Au systems as experimentally measured or calculated by density functional theory. We also fit defect formation energies, surface energies and stacking fault energies for Pt and Au metals. The resulting potentials are used to map a 2D contour of the gamma surface and simulate the tensile test of 16-grain polycrystalline Pt and Au structures at 300 K. The stress-strain behaviour is investigated and the primary slip systems {1 1 1}〈1 [Formula: see text] 0〉 are identified. In addition, we perform high temperature (1800 K for Au and 2300 K for Pt) molecular dynamics simulations of 30 nm Pt and Au truncated octahedron nanoparticles and examine morphological changes of each particle. We further calculate the activation energy barrier for surface diffusion during simulations of several nanoseconds and report energies of [Formula: see text] eV for Pt and [Formula: see text] eV for Au. This initial parameterization and application of the Pt and Au potentials demonstrates a starting point for the extension of these potentials to multicomponent systems within the COMB3 framework.


Influence of the synthetic method on the properties of two-photon-sensitive mesoporous silica nanoparticles.
Herein we report the modulation of the properties of mesoporous silica nanoparticles (NPs) via various synthetic approaches. Three types of elaborations were compared, one in aqueous media at 25 °C, and the other two at 80 °C in water or in a water-ethanol mixture. For all these methods, an alkoxysilylated two-photon photosensitizer (2PS) was co-condensed with tetraethylorthosilicate (TEOS) in the presence of cetyltrimethylammonium bromide (CTAB), leading to five two-photon-sensitive mesoporous silica (M2PS) NPs. The M2PS NP porous structure could be tuned from radial to worm-like and MCM-41 types of organization. Besides, the 2PS precursor spatial dispersion was found to be highly dependent on both the 2PS initial concentration and the elaboration process. As a result, two-photon properties were modulated by the choice of the synthesis, the best results being found in aqueous media at 25 or 80 °C. Finally, the M2PS NPs were used for in vitro two-photon imaging of cancer cells.


Competitive adsorption: a physical model for lung surfactant inactivation.
Charged, surface-active serum proteins can severely reduce or eliminate the adsorption of lung surfactant from the subphase to the alveolar air-liquid interface via a kinetically controlled competitive adsorption process. The decreased surfactant concentration at the interface leads to higher surface tensions during the compression of the interface during breathing. The correspondence between the factors governing colloid stability and competitive adsorption is validated via a new method of measuring surfactant and serum protein adsorption rates to the air-water interface, using quantitative Brewster angle microscopy (BAM). Competitive adsorption from a 10 mg/mL albumin subphase prevents the adsorption of lung surfactant from even high subphase concentrations due to the fast diffusion of the water-soluble proteins to the interface. The formation of an albumin film causes an electrostatic and steric barrier to subsequent surfactant adsorption, which can destroy the necessary properties of functional lung surfactant: low surface tension during compression and rapid respreading after film collapse. Surfactant inactivation is at least partially due to decreased surfactant adsorption; such decreased adsorption due to the presence of serum proteins may play a role in the development and severity of acute respiratory distress syndrome.


Suckling-induced activation of neuronal input to the dorsomedial nucleus of the hypothalamus: possible candidates for mediating the activation of DMH neuropeptide Y neurons during lactation.
Activation of the neuropeptide Y (NPY) neuronal system in the dorsomedial nucleus of the hypothalamus (DMH) during lactation in the rat is in part due to neural impulses arising from the suckling stimulus. However, the afferent neuronal input to the DMH that is activated during lactation and is responsible for activation of NPY neurons is currently unknown. Previously, using cFos as a marker for neuronal activation, we identified several brain areas in the lactating animals that were activated by the suckling stimulus. Thus, the objective of the present study was to determine if any of these suckling activated areas project directly to the DMH. The retrograde tracer, fluorogold (FG), was injected into the DMH on day 4 postpartum. FG-injected lactating rats were then deprived of their eight-pup litters on day 9 postpartum, and 48 h later, the pups were returned to the females to reinitiate the suckling stimulus for 90 min and induce cFos expression. The animals were then perfused and the brains were subjected to double-label immunohistochemistry to visualize both FG- and cFos-positive cells. Substantial numbers of FG/cFos double-labeled cells were found in forebrain regions, including the preoptic area, lateral septal nucleus, ventral subiculum, and supramammillary nucleus, and in brainstem regions, including the lateral parabrachial nucleus, periaqeductal gray, and ventrolateral medulla. In conclusion, these areas are potentially important candidates for mediating the activation of the NPY neuronal system in the DMH during lactation.


[Breath-analysis tests in gastroenetrological diagnosis].
The introduction of a simple method for analysis of 14CO2 in breath allowed a more widely application of breath-tests in the diagnosis of gastroenterological diseases. During a breath-test a 14C-labelled compound is administered orally and 14CO2 is subsequently measured in breath by discontinuous samplings of 14CO2 by virtue of a trapping solution (hyamine hydroxide). Most helpful tests in gastroenterology are the 14C-glycyl-cholate breath test for detecting increased deconjugation of bile acids due to small intestinal bacterial overgrowth or bile acid malabsorption in ileal resection or Crohn's disease of the ileum, the 14C-lactose breath test in lactase deficiency, whereas the 14C-tripalmitin test seems less helpful in the diagnosis of fat malabsorption. A 14C-aminopyrine breath test may turn out to be a simple and valuable liver function test. Oral loading tests with breath analysis of H2 have shown to be helpful in the diagnosis of carbohydrate malabsorption, determination of intestinal transit time and intestinal gas production. Due to technical reasons (gas-chromatographie analysis) H2-breath analysis is still limited to research centers. Despite low radiation doses after oral administration of 14C-labelled compounds oral loading tests with H2- or 13C-analysis might be preferable in the future.


fMRI evidence of aberrant neural adaptation for objects in schizophrenia and bipolar disorder.
Functional magnetic resonance imaging (fMRI) adaptation (also known as fMRI repetition suppression) has been widely used to characterize stimulus selectivity in vivo, a fundamental feature of neuronal processing in the brain. We investigated whether SZ patients and BD patients show aberrant fMRI adaptation for object perception. About 52 SZ patients, 55 BD patients, and 53 community controls completed an object discrimination task with three conditions: the same object presented twice, two exemplars from the same category, and two exemplars from different categories. We also administered two functional localizer tasks. A region of interest analysis was employed to evaluate a priori hypotheses about the lateral occipital complex (LOC) and early visual cortex (EVC). An exploratory whole brain analysis was also conducted. In the LOC and EVC, controls showed the expected reduced fMRI responses to repeated presentation of the same objects compared with different objects (i.e., fMRI adaptation for objects, p < .001). SZ patients showed an adaptation effect that was significantly smaller compared with controls. BD patients showed a lack of fMRI adaptation. The whole brain analyses showed enhanced fMRI responses to repeated presentation of the same objects only in BD patients in several brain regions including anterior cingulate cortex. This study was the first to employ fMRI adaptation for objects in SZ and BD. The current findings provide empirical evidence of aberrant fMRI adaptation in the visual cortex in SZ and BD, but in distinctly different ways.


Thiol-Cyanobenzothiazole Ligation for the Efficient Preparation of Peptide-PNA Conjugates.
Antisense oligonucleotide (ASO)-based drugs are emerging with great potential as therapeutic compounds for diseases with unmet medical needs. However, for ASOs to be effective as clinical entities, they should reach their intracellular RNA and DNA targets at pharmacologically relevant concentrations. Over the past decades, various covalently attached delivery vehicles have been utilized for intracellular delivery of ASOs. One such approach is the use of biocompatible cell-penetrating peptides (CPPs) covalently conjugated to ASOs. The stability of the linkage is of paramount importance for maximal intracellular delivery to achieve the desired therapeutic effect. In this study, we have investigated the efficiency and stability of four different bioorthogonal and nonreductive linkages including triazole, thioether, thiosuccinimide thioether and thiazole moieties. Here we have shown that thiazole and thiosuccinimide are the two most efficient and facile approaches for the preparation of peptide-ASO conjugates. The thiazole linkage had a higher stability compared to the thiosuccinimide thioether at physiological conditions (pH 7.4, 37 °C) in the presence of a biologically relevant concentration of glutathione. We have also shown that the peptide-ASO conjugate with a thiosuccinimide linkage has a significantly lower antisense activity compared to the peptide-ASO with the thiazole linkage, which maintains its antisense activity after 24 h of exposure to glutathione. In summary, we have demonstrated that the bioorthogonal thiazole linkage offers the benefits of mild reaction conditions, fast reaction kinetics, absence of any byproducts, and higher stability compared to other conjugation approaches. This facile ligation can be used for the synthesis of a variety of bioconjugates where a stable linkage is required.


One-step hydrothermal synthesis of chiral carbon dots and their effects on mung bean plant growth.
Chiral compounds/materials have important effects on the growth of plants. Chiral carbon dots (CDs), as an emerging chiral carbon nanomaterial, have great potential in bio-application and bio-nanotechnology. Herein, we report a hydrothermal method to synthesize chiral CDs from cysteine (cys) and citric acid. These chiral CDs were further demonstrated to have systemic effects on the growth of mung bean plants, in which case both l- and d-CDs can promote the growth of the root in mung bean plants, stem length of mung bean sprouts and water absorption of bean seeds. The elongation of mung bean sprouts presented an increasing trend with the treatment of chiral CDs of increasing concentration (below 500 μg mL-1). Furthermore, in the optimal concentration (100 μg mL-1), the l-CDs can improve root vigor and the activity of the Rubisco enzyme of bean sprouts by 8.4% and 20.5%, while the d-CDs increased by 28.9% and 67.5%. Due to more superior properties in improving root vigor and the activity of the Rubisco enzyme of mung bean sprouts, d-CDs are able to enhance photosynthesis better and accumulate more carbohydrate in mung bean plants.


Genetics and function of the capsules of Burkholderia pseudomallei and their potential as therapeutic targets.
Burkholderia pseudomallei is the causative agent of melioidosis, a fatal disease that is endemic to Southeast Asia and northern Australia. The clinical manifestations of melioidosis may range from an acute pneumonia or acute septicemia, to chronic and latent infections. B. pseudomallei is inherently resistant to a number of antibiotics, and even with aggressive antibiotic therapy, the mortality rate remains high, and the incidence of relapse is common. The resistance of this organism to a number of antibiotics has created a need for the development of other therapeutic strategies, including the identification of novel therapeutic targets. B. pseudomallei has been shown to produce a number of capsular polysaccharides, one of which has been shown to contribute to the virulence of the organism. The structures of these polysaccharides have been determined and the genes encoding for the biosynthesis of one of the capsular polysaccharides (CPS I) have been identified. Analysis of the genome sequence of this organism has revealed the presence of three other capsule gene clusters that may encode for the chemical structures previously identified. Since one of the capsules produced by B. pseudomallei has been shown to be important in virulence, the genes encoding for the proteins responsible for its biosynthesis may be considered as potential targets.


ATM-dependent activation of SIM2s regulates homologous recombination and epithelial-mesenchymal transition.
There is increasing evidence that genomic instability is a prerequisite for cancer progression. Here we show that SIM2s, a member of the bHLH/PAS family of transcription factors, regulates DNA damage repair through enhancement of homologous recombination (HR), and prevents epithelial-mesenchymal transitions (EMT) in an Ataxia-telangiectasia mutated (ATM)-dependent manner. Mechanistically, we found that SIM2s interacts with ATM and is stabilized through ATM-dependent phosphorylation in response to IR. Once stabilized, SIM2s interacts with BRCA1 and supports RAD51 recruitment to the site of DNA damage. Loss of SIM2s through the introduction of shSIM2 or the mutation of SIM2s at one of the predicted ATM phosphorylation sites (S115) reduces HR efficiency through disruption of RAD51 recruitment, resulting in genomic instability and induction of EMT. The EMT induced by the mutation of S115 is characterized by a decrease in E-cadherin and an induction of the basal marker, K14, resulting in increased invasion and metastasis. Together, these results identify a novel player in the DNA damage repair pathway and provides a link in ductal carcinoma in situ progression to invasive ductal carcinoma through loss of SIM2s, increased genomic instability, EMT, and metastasis.


Air Versus Sulfur Hexafluoride Gas Tamponade in Descemet Membrane Endothelial Keratoplasty: A Fellow Eye Comparison.
To perform a fellow eye comparison of outcomes and complications when using air or sulfur hexafluoride (SF6) gas as a tamponade in Descemet membrane endothelial keratoplasty (DMEK). One hundred thirty-six eyes of 68 consecutive patients who underwent uneventful DMEK in both eyes for Fuchs endothelial corneal dystrophy were included in this retrospective study. Inclusion criteria were air tamponade (80% of the anterior chamber volume) in the first eye and 20% SF6 gas tamponade (80% of the anterior chamber volume) in the second eye; and same donor tissue culture condition in both eyes. All eyes received laser iridotomy on the day before DMEK. Main outcome measures included preoperative and postoperative best-corrected visual acuity, endothelial cell density, corneal volume, rebubbling rate, and rate of postoperative pupillary block caused by the air/gas bubble. Thirteen of 68 eyes (19.1%) with an air tamponade needed rebubbling compared with 4 of 68 eyes (5.9%) with an SF6 gas tamponade (P = 0.036). Postoperative pupillary block necessitating partial release of air/gas occurred in 1 eye (1.5%) with an air tamponade and 3 eyes (4.4%) with an SF6 gas tamponade (P = 0.301). There were no significant differences in preoperative and postoperative best-corrected visual acuity, endothelial cell density, and corneal volume within 3-month follow-up. Our results confirm the previously reported better graft adhesion when using an SF6 gas tamponade in DMEK without increased endothelial cell toxicity. The rate of pupillary block in eyes with an SF6 gas tamponade was comparable to that with an air tamponade. As a consequence, we recommend using SF6 gas as the tamponade in DMEK.


Conservation and expression of PIWI-interacting RNA pathway genes in male and female adult gonad of amniotes.
The PIWI-interacting RNA (piRNA) pathway is essential for germline development and transposable element repression. Key elements of this pathway are members of the piRNA-binding PIWI/Argonaute protein family and associated factors (e.g., VASA, MAELSTROM, and TUDOR domain proteins). PIWI-interacting RNAs have been identified in mouse testis and oocytes, but information about the expression of the different piRNA pathway genes, in particular in the mammalian ovary, remains incomplete. We investigated the evolution and expression of piRNA pathway genes in gonads of amniote species (chicken, platypus, and mouse). Database searches confirm a high level of conservation and revealed lineage-specific gain and loss of Piwi genes in vertebrates. Expression analysis in mammals shows that orthologs of Piwi-like (Piwil) genes, Mael (Maelstrom), Mvh (mouse vasa homolog), and Tdrd1 (Tudor domain-containing protein 1) are expressed in platypus adult testis. In contrast to mouse, Piwil4 is expressed in platypus and human adult testis. We found evidence for Mael and Piwil2 expression in mouse Sertoli cells. Importantly, we show mRNA expression of Piwil2, Piwil4, and Mael in oocytes and supporting cells of human, mouse, and platypus ovary. We found no Piwil1 expression in mouse and chicken ovary. The conservation of gene expression in somatic parts of the gonad and germ cells of species that diverged over 800 million yr ago indicates an important role in adult male and female gonad.


Co-composting of horticultural waste with fruit peels, food waste, and soybean residues.
Horticultural waste was co-composted with fruit peels, food waste, and soybean residues individually to evaluate the effects of these easily available organic wastes in Singapore on the composting process and product quality. Each co-composting material was mixed with horticultural waste in the wet weight ratio of 1:1 and composted for 46 days. Results showed that all co-composting materials accelerated the degradation of total carbon and resulted in higher nutrients of nitrogen (N), phosphorous (P), and potassium (K) in the final product compared with horticultural waste alone. Mixture with fruit peels achieved the fastest total carbon loss; however, did not reach the minimum required temperature for pathogen destruction. The end product was found to be the best source for K and had a higher pH that could be used for the remediation of acidic soil. Food waste resulted in the highest available nitrate (NO3-N) content in the end product, but caused high salt content, total coliforms, and slower total carbon loss initially. Soybean residues were found to be the best co-composting material to produce compost with high N, P, and K when compared with other materials due to the highest temperature, fastest total carbon loss, fastest reduction in C/N ratio, and best conservation of nutrients.


Metal-containing organic compounds for memory and data storage applications.
With the upcoming trend of Big Data era, some new types of memory technologies have emerged as substitutes for the traditional Si-based semiconductor memory devices, which are encountering severe scaling down technical obstacles. In particular, the resistance random access memory (RRAM) and magnetic random access memory (MRAM) hold great promise for the in-memory computing, which are regarded as the optimal strategy and pathway to solve the von Neumann bottleneck by high-throughput in situ data processing. As far as the active materials in RRAM and MRAM are concerned, organic semiconducting materials have shown increasing application perspectives in memory devices due to their rich structural diversity and solution processability. With the introduction of metal elements into the backbone of molecules, some new properties and phenomena will emerge accordingly. Consequently, the RRAM and MRAM devices based on metal-containing organic compounds (including the small molecular metal complexes, metallopolymers, metal-organic frameworks (MOFs) and organic-inorganic-hybrid perovskites (OIHPs)) have been widely explored and attracted intense attention. In this review, we highlight the fundamentals of RRAM and MRAM, as well as the research progress of the applications of metal-containing organic compounds in both RRAM and MRAM. Finally, we discuss the challenges and future directions for the research of organic RRAM and MRAM.


Acute respiratory failure and the kinetics of neutrophil recovery in pediatric hematopoietic cell transplantation: a multicenter study.
In this multicenter study, we investigated the kinetics of neutrophil recovery in relation to acuity and survival among 125 children undergoing allogeneic hematopoietic cell transplantation (allo-HCT) who required invasive mechanical ventilation (IMV). Recovery of neutrophils, whether prior to or after initiation of IMV, was associated with a significantly decreased risk of death relative to never achieving neutrophil recovery. A transient increase in acuity (by oxygenation index and vasopressor requirements) occurred among a subset of the patients who achieved neutrophil recovery after initiation of IMV; 61.5% of these patients survived to discharge from the intensive care unit (ICU). Improved survival among patients who subsequently achieved neutrophil recovery on IMV was not limited to those with peri-engraftment respiratory distress syndrome. The presence of a respiratory pathogen did not affect the risk of death while on IMV but was associated with an increased length of IMV (p < 0.01). Among patients undergoing HCT who develop respiratory failure and require advanced therapeutic support, neutrophil recovery at time of IMV and/or presence of a respiratory pathogen should not be used as determining factors when counseling families about survival.


A hybrid approach to regime shift detection.
In this article, we propose a method for the analysis of regime shifts in frequency data. This method identifies those points in the development of a process for which deviations are most extreme. Based on a statistical model, functions are estimated that describe the process. This description can represent either the entire series of scores or the series before and after a shift point. The shift point can be either given a priori or estimated from the data. The method is hybrid in that it first uses standard models for the estimation of parameters of the process that is examined and then, in a second step, elements of Configural Frequency Analysis. Uni- and multivariate versions of the method are proposed. In data examples, road traffic data from California and Germany are analyzed before and after particular shift points. Extensions of the proposed method are discussed.


A novel imaging technology to assess tissue oxygen saturation and its correlation with indocyanine green in the gastric conduit during thoracic esophagectomy.
Anastomotic leakage in esophagectomy is a serious complication, and assessing blood perfusion in the conduit can help minimize this risk. Indocyanine green is the most widely used method to assess tissue blood flow; however, this technique has disadvantages. Evaluating tissue oxygen saturation in the gastric conduit during thoracic esophagectomy compared with indocyanine green blood perfusion assessment addresses these disadvantages and can be performed easily and repeatedly. This was a prospective study of patients with esophageal cancer who underwent thoracic esophagectomy. Intraoperative tissue oxygen saturation and indocyanine green measurements were obtained to determine the anastomotic site and to compare the correlation between the 2 methods. Tissue oxygen saturation and indocyanine green values were obtained at the tip of the gastric conduit, the demarcation line indicating visible perfusion, and the end of the right gastroepiploic artery. Fifty-seven patients were enrolled in this study; 3 developed anastomotic leakage, and all 3 underwent robotic thoracic surgery. The tissue oxygen saturation value decreased gradually toward the tip of the conduit, as did congestion, and was significantly decreased at the tip compared with the value at the demarcation line (P = .001). Mean tissue oxygen saturation differed significantly between the leakage and no-leakage groups at the anastomosis site (P = .04). We found a negative correlation between tissue oxygen saturation and indocyanine green values at the end of the right gastroepiploic artery (r = -0.361; P = .03). Tissue oxygen saturation imaging was useful in determining the anastomotic site and addressed the disadvantages associated with indocyanine green.


Short-Term and Long-Term Effects after Exposure to Ionizing Radiation and Visible Light on Retina and Retinal Pigment Epithelium of Mouse Eye.
A comparative in vivo study of the effects of ionizing radiation (accelerated protons) and visible light (400-700 nm) on the retina and retinal pigment epithelium (RPE) of the mouse eye was carried out. Using the methods of fluorescence spectroscopy and high-performance liquid chromatography (HPLC), we analyzed the relative composition of retinoids in chloroform extracts obtained from the retinas and RPEs immediately after exposure of animals to various types of radiation and 4.5 months after they were exposed and maintained under standard conditions throughout the period. The fluorescent properties of chloroform extracts were shown to change upon exposure to various types of radiation. This fact indicates the accumulation of retinoid oxidation and degradation products in the retina and RPE. The data from fluorescence and HPLC analyses of retinoids indicate that when exposed to ionizing radiation, retinoid oxidation processes similar to photooxidation occur. Both ionizing radiation and high-intensity visible light have been shown to be characterized by long-term effects. The action of any type of radiation is assumed to activate the mechanism of enhanced reactive oxygen species production, resulting in a long-term damaging effect.


Mechanisms of coronavirus cell entry mediated by the viral spike protein.
Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis. It is classified as a class I fusion protein, and is responsible for binding to the receptor on the host cell as well as mediating the fusion of host and viral membranes-A process driven by major conformational changes of the S protein. This review discusses coronavirus entry mechanisms focusing on the different triggers used by coronaviruses to initiate the conformational change of the S protein: receptor binding, low pH exposure and proteolytic activation. We also highlight commonalities between coronavirus S proteins and other class I viral fusion proteins, as well as distinctive features that confer distinct tropism, pathogenicity and host interspecies transmission characteristics to coronaviruses.


Pursue today and assess tomorrow - how students' subjective perceptions influence their preference for self- and peer assessments.
Alternative assessments engage students in the assessment process to improve both short- and long-term outcomes by developing their judgments and responsibility about their own learning, and that of their peers. In this study, we investigated students' perception towards self- and peer-assessment, their objectivity and impact on students' learning. The study was conducted at the Medical University of Vienna. Attitudes of second year undergraduate medical students towards self- and peer-assessment, and their objectivity, appropriateness, and the impact of these assessments on students' learning activities, was inquired using a self-developed questionnaire. Four hundred twenty-three students participated in this study. Self-assessment was found more appropriate method to assess students' knowledge. Most of students agreed that peer-assessment is not objective (M = - 0.07). Majority of students evaluated that peer assessment has no or little impact on their active and passive learning (M = - 0.23, - 0.35), on the other hand self-assessment was reported as a helpful tool for gaining long-term knowledge (M = 0.13) and following the content of courses (M = 0.16). Based on our results, students' perspective on peer assessment were negative, on the whole, students had positive attitudes towards self-assessment and negative attitudes towards peer-assessment. This study also determined that self-assessment leads to the promotion of students' learning.


The formation of threo-11-hydroxy-trans-12: 13-epoxy-9-cis-octadecenoic acid by enzymic isomerisation of 13-L-hydroperoxy-9-cis, 11-transoctadecadienoic acid by soybean lipoxygenase-1.
The interaction of soybean lipoxygenase-1 with 13-L-hydroperoxy-9-cis, 11-trans-octadecadienoic acid (13-hydroperoxy-linoleate), the product of the enzymic dioxygenation of linoleic acid, yields either a yellow or a purple-coloured enzyme species depending on the amount of product used. With an excess of 13-hydroperoxy-linoleate a labile purple-coloured enzyme species is formed which reverts to a yellow-coloured form with concomitant conversion of the hydroperoxy compound. In this reaction 13-hydroperoxy-linoleate isomerises into threo-11-hydroxy-trans-12:13 epoxy-9-cis-octadecenoic acid as could be concluded from nuclear magnetic resonance and mass spectral data. Experiments with 13-[18O2]hydroperoxy-linoleate showed a high retention (70%) of the 2 hydroperoxy oxygen atoms in the end product.


Molecular profiling of single cells in response to mechanical force: comparison of chondrocytes, chondrons and encapsulated chondrocytes.
A chondrocyte and its surrounding pericellular matrix (PCM) are defined as a chondron. The PCM plays a critical role in enhancing matrix production, protecting the chondrocyte during loading and transducing mechanical signals. Tissue engineering involves the design of artificial matrices which aim to mimic PCM function for mechanical strength and signalling motifs. We compare the mechanical performance and mechanoresponsiveness of chondrocytes with and without PCM, and encapsulated by alternate adsorption of two oppositely charged polyelectrolytes; chitosan and hyaluronan. Zeta potential measurements confirmed the success of the encapsulation. Encapsulation did not influence chondrocyte viability or metabolic activity. Cells were compressed by micromanipulation with final deformations to 30%, 50% and 70%. Force-displacement data showed that the larger the deformation at the end of compression, the greater the force on the cell. Mechanoresponsiveness of cells was studied by combining single cell PCR with dynamic compression at 20% and 40%. Aggrecan and Type II collagen gene expression were significantly increased in encapsulated chondrocytes and chondrons compared to chondrocytes whereas dynamic compression had no effect on SOX9 or lubricin gene expression. Our results demonstrate that although encapsulation can mimic responses of chondrocytes to biomechanical compression the molecular profile did not reach the enhanced levels observed with chondrons.


Balance of trade: export-import in family medicine.
North American family physicians leaving for less-developed countries (LDCs) may not be aware of internationally validated diagnostic and treatment technologies originating in LDCs. Thus they may bring with them inappropriate models and methods of medical care. More useful "exports" are based in sharing our collaborative vocational perspective with dedicated indigenous generalist clinicians who serve their communities. More specifically, Western doctors abroad can promote local reanalyses of international evidence-based medicine (EBM) studies, efficient deployment of scarce clinical resources, and a family medicine/generalist career ladder, ultimately reversing the "brain drain" from LDCs. Balancing these exports, we should import the growing number of EBM best practices originated in World Health Organization and other LDCs research that are applicable in developed nations. Many generalist colleagues, expatriate and indigenous, with long-term LDC experience stand ready to help us import these practices and perspectives.


Spatial variation and density-dependent dispersal in competitive coexistence.
It is well known that dispersal from localities favourable to a species' growth and reproduction (sources) can prevent competitive exclusion in unfavourable localities (sinks). What is perhaps less well known is that too much emigration can undermine the viability of sources and cause regional competitive exclusion. Here, I investigate two biological mechanisms that reduce the cost of dispersal to source communities. The first involves increasing the spatial variation in the strength of competition such that sources can withstand high rates of emigration; the second involves reducing emigration from sources via density-dependent dispersal. I compare how different forms of spatial variation and modes of dispersal influence source viability, and hence source-sink coexistence, under dominance and pre-emptive competition. A key finding is that, while spatial variation substantially reduces dispersal costs under both types of competition, density-dependent dispersal does so only under dominance competition. For instance, when spatial variation in the strength of competition is high, coexistence is possible (regardless of the type of competition) even when sources experience high emigration rates; when spatial variation is low, coexistence is restricted even under low emigration rates. Under dominance competition, density-dependent dispersal has a strong effect on coexistence. For instance, when the emigration rate increases with density at an accelerating rate (Type III density-dependent dispersal), coexistence is possible even when spatial variation is quite low; when the emigration rate increases with density at a decelerating rate (Type II density-dependent dispersal), coexistence is restricted even when spatial variation is quite high. Under pre-emptive competition, density-dependent dispersal has only a marginal effect on coexistence. Thus, the diversity-reducing effects of high dispersal rates persist under pre-emptive competition even when dispersal is density dependent, but can be significantly mitigated under dominance competition if density-dependent dispersal is Type III rather than Type II. These results lead to testable predictions about source-sink coexistence under different regimes of competition, spatial variation and dispersal. They identify situations in which density-independent dispersal provides a reasonable approximation to species' dispersal patterns, and those under which consideration of density-dependent dispersal is crucial to predicting long-term coexistence.


Dialysis and a plant-based diet to achieve physiologic urea levels for fetal benefit: Normal pregnancy outcome despite chronic kidney disease and hypertension.
Chronic kidney disease significantly increases the risk of adverse maternal and perinatal outcomes. A growing body of evidence suggests that intensive dialysis, achieving physiologic pre-dialysis blood urea, is associated with decreased morbidity. We report a case of a successful pregnancy outcome in a 32-year-old nulliparous woman with stage 4 chronic kidney disease who underwent haemodialysis from 11 to 31 weeks' gestation for fetal benefit and concurrently trialled a plant-based diet. We hypothesise that her dietary changes assisted with urea reduction, enabling her to become dialysis independent. Although we must recognise that such pregnancies remain high risk, as demonstrated both in this case and more recent literature, advances in complex obstetric care and dialysis protocols may now give women with chronic kidney disease a realistic hope of a successful pregnancy.


Parental Psychological Flexibility as a Mediating Factor of Post-Traumatic Stress Disorder in Children after Hospitalization or Surgery.
Illness, surgery, and surgical hospitalization are significant stressors for children. Children exposed to such medical events may develop post-traumatic medical syndrome (PMTS, pediatric medical traumatic stress) that could slow their physical and emotional recovery. This study examined the relationship between the level of parental psychological resilience and the development of PMTS in young children. We surveyed 152 parents of children aged 1-6 who were admitted to the pediatric surgery department. Parents completed questionnaires in two phases. In the first phase, one of the parents completed the Acceptance and Action Questionnaire (AAQ-ll) and the Parental Psychological Flexibility (PPF) Questionnaire. In the second phase, about three months after discharge, the same parent completed the Young Child PTSD (Post Traumatic Stress Disorder) Checklist (YCPC) and the UCLA (Los Angeles, CA, USA) PTSD Reaction Index for DSM-5 Parent/Caregiver Version for Children Age 6 Years and Younger Evaluating Post-traumatic Disorder. In addition, the parent completed a Posttraumatic Stress Diagnostic Scale (PDS) questionnaire to assess the existence of post-traumatic symptoms in the parents. The findings indicate that (1) a parent's psychological flexibility is significantly associated with the level of personal distress (r = -0.45, p < 0.001), (2) a parents' level of distress is significantly correlated with the child's level of PTMS, and (3) a parent's level of psychological flexibility is a significant mediating factor between the level of parental post-traumatic distress and the child's level of PTMS. A parent's psychological flexibility may act as a protective factor against the development of the child's mental distress after hospitalization or surgery.


Surgical management of Pott's disease of the spine in pediatric patients: A single surgeon's experience of 8 years in a tertiary care center.
A retrospective, case study of 64 pediatric patients who underwent spinal surgery for Pott's spine and have minimum 6 months follow-up. The aim of this study was to evaluate the surgical management and outcome of 64 pediatric Pott's spine cases operated by single surgeon over last 8 years, with a minimum follow-up of 6 months. The prognostic significance and the outcome of the demographic factors, location of the disease, and its surgical approach were also evaluated in these patients. The data collected retrospectively from the institute's record case sheets of the 64 pediatric patients with Pott's disease of the spine, operated between 2002 and 2010 in the Department of Neurosurgery, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, were analyzed. The study population consisted of 40 male and 24 female pediatric patients. Clinical findings included back pain, paraparesis, kyphosis, fever, sensory disturbance, and bowel and bladder dysfunction. The most common region of Pott's disease was the thoracic region [21/64 (33%)] followed by craniovertebral junction (CVJ) [17/64 (27%)]. At presentation, all of the patients had neurological features of spinal cord compression. All patients were treated with antituberculous chemotherapy which was continued after the surgical intervention also. Transthoracic surgical approach [18/64 (28%)] was the most frequently required surgery followed by transoral decompression with posterior fusion [12/64 (19%)] depending on the site of disease and compression of neuraxis. Initially, more than two-third of the patients were in poor grade of Kumar and Kalra scoring as well as modified Kumar and Kalra scoring, which were reduced to about one fifth after the surgical intervention, and the outcome was good as the condition of 46 patients (72%) improved significantly. Currently, treatment of spinal tubercular infections requires a multidisciplinary team that includes infectious diseases experts, neuroradiologists, and spine surgeons. The key to successful management is early detection and timely and judicious surgical intervention, the decision of which needs to be taken in view of clinicoradiological compression of the spinal cord and nerve roots, age of the patient and responsiveness of ATT.


Urinary biomarkers of catechins and risk of hepatocellular carcinoma in the Shanghai Cohort Study.
Dietary catechins are phytochemicals with both antioxidative and prooxidative stress properties. Green tea is a major source of catechins and may be associated with hepatocellular carcinoma (HCC) risk, but the catechin-HCC relationship has not been evaluated using a biomarker-based approach. A nested case-control study of HCC (211 cases and 1,067 matched controls) was conducted within the Shanghai Cohort Study, which enrolled 18,244 men between 1986 and 1989. Concentrations of specific catechins, including epicatechin, epigallocatechin (EGC), and 4'-O-methyl-epigallocatechin, were measured in urine specimens that had been collected prior to HCC diagnosis. None of the catechins measured were associated with HCC risk. In stratified analyses, there was a statistically significant trend for an association of higher urinary EGC with increased HCC risk among subjects with positive serology for hepatitis B surface antigen (P for trend = 0.02). This positive EGC-HCC association became stronger for hepatitis B surface antigen-positive persons who also had low serum retinol levels (for detectable levels vs. undetectable levels, odds ratio = 2.62, 95% confidence interval: 1.25, 5.51). There was no evidence supporting a protective role of catechins in the development of HCC. Instead, exposure to high levels of catechins may increase the risk of developing HCC for high-risk individuals.


Analysis of responses to sarafotoxin 6a and sarafotoxin 6c in the pulmonary vascular bed of the cat.
Pulmonary vascular responses to sarafotoxins 6a and 6c (S6a and S6c) were investigated in the intact-chest cat under constant flow conditions. Injections of S6a and S6c into the perfused lobar artery caused dose-related increases in lobar arterial pressure, increased left atrial pressure, and produced biphasic changes in systemic arterial (aortic) pressure. When left atrial pressure was maintained constant, injections of S6a, S6c, and endothelin 1 (ET-1) caused dose-related increases in lobar arterial pressure. The increases in lobar arterial pressure in response to S6a and S6c were not altered by treatment with a cyclooxygenase inhibitor or a thromboxane receptor blocking agent. Increases in lobar arterial pressure in response to S6a and S6c were not altered when airflow to the left lower lung lobe was interrupted by bronchial occlusion, and pressor responses were not diminished when the left lower lobe was perfused with low-molecular-weight dextran. Under conditions of controlled blood flow and constant left atrial pressure, S6a, S6b, S6c, and ET-1 had similar pressor activity, whereas the thromboxane A2 mimic, U-46619, had far greater activity when compared on a nanomolar basis. The present studies demonstrate that S6a and S6c have significant vasoconstrictor activity in the feline pulmonary vascular bed. These data suggest that pulmonary vasoconstrictor responses to the endothelin peptides are not dependent on release of cyclooxygenase products and the activation of thromboxane A2 receptors, alterations in bronchomotor tone, or interaction with formed elements in blood.


Efficacy of N-Acetylcysteine, Glutathione, and Ascorbic Acid in Acute Toxicity of Paraoxon to Wistar Rats: Survival Study.
There are a great number of reports with assertions that oxidative stress is produced by organophosphorus compound (OPC) poisoning and is a cofactor of mortality and morbidity in OPC toxicity. In addition, antioxidants have been suggested as adjuncts to standard therapy. However, there is no substantial evidence for the benefit of the use of antioxidants in survival after acute intoxication of OPCs. The present study was conducted to assess the effectiveness of three non-enzymatic antioxidants (NEAOs), N-acetylcysteine (NAC), glutathione (GSH), and ascorbic acid (AA), in acute intoxication of adult male Wister rats with paraoxon. The efficacy of the antioxidants was estimated as both a pretreatment and a concurrent application along with the standard oxime, pralidoxime (2-PAM). Relative risk of death after 48 hours of application was estimated by Cox regression analysis. The results revealed no benefit of either tested NEAO to the improvement in survival of experimental rats. The application of these antioxidants was found to be deleterious when administered along with pralidoxime compared to the treatment with pralidoxime alone. It has been concluded that the tested non-enzymatic antioxidants are not useful in acute toxicity for improving survival rates. However, the individual toxic dynamics of diversified OPCs should not be overlooked and further studies with different OPCs are suggested.


Perceived stress and resilience in Alzheimer's disease caregivers: testing moderation and mediation models of social support.
The study examined whether social support functioned as a protective, resilience factor among Alzheimer's disease (AD) caregivers. Moderation and mediation models were used to test social support amid stress and resilience. A cross-sectional analysis of self-reported data was conducted. Measures of demographics, perceived stress, family support, friend support, overall social support, and resilience were administered to caregiver attendees (N=229) of two AD caregiver conferences. Hierarchical regression analysis showed the compounded impact of predictors on resilience. Odds ratios generated probability of high resilience given high stress and social supports. Social support moderation and mediation were tested via distinct series of regression equations. Path analyses illustrated effects on the models for significant moderation and/or mediation. Stress negatively influenced and accounted for most variation in resilience. Social support positively influenced resilience, and caregivers with high family support had the highest probability of elevated resilience. Moderation was observed among all support factors. No social support fulfilled the complete mediation criteria. Evidence of social support as a protective, moderating factor yields implications for health care practitioners who deliver services to assist AD caregivers, particularly the promotion of identification and utilization of supportive familial and peer relations.


Effects of stroke on informal carers.
Informal carers have a pivotal role in caring for patients who have had a stroke. Research has shown that informal carers have unmet information, psychological and social needs. There is a lack of research about how informal carers in Northern Ireland manage the role of caring for a patient who has experienced stroke, and what kind of support they need and receive. This literature review explores the experiences of informal carers providing stroke care in the home. The issues highlighted in the article are relevant worldwide, because the incidence of stroke is increasing in developed and developing countries.


Ribosome-associated vesicles: A dynamic subcompartment of the endoplasmic reticulum in secretory cells.
The endoplasmic reticulum (ER) is a highly dynamic network of membranes. Here, we combine live-cell microscopy with in situ cryo-electron tomography to directly visualize ER dynamics in several secretory cell types including pancreatic β-cells and neurons under near-native conditions. Using these imaging approaches, we identify a novel, mobile form of ER, ribosome-associated vesicles (RAVs), found primarily in the cell periphery, which is conserved across different cell types and species. We show that RAVs exist as distinct, highly dynamic structures separate from the intact ER reticular architecture that interact with mitochondria via direct intermembrane contacts. These findings describe a new ER subcompartment within cells.


Wavefront shaping enhanced Raman scattering in a turbid medium.
Spontaneous Raman scattering is a powerful tool for chemical sensing and imaging but suffers from a weak signal. In this Letter, we present an application of adaptive optics to enhance the Raman scattering signal detected through a turbid, optically thick material. This technique utilizes recent advances in wavefront shaping techniques for focusing light through a turbid media and applies them to chemical detection to achieve a signal enhancement with little sacrifice to the overall simplicity of the experimental setup. With this technique, we demonstrate an enhancement in the Raman signal from titanium dioxide particles through a highly scattering material. This technique may pave the way to label-free tracking using the optical memory effect.


Unraveling Molecular Mechanisms of THAP1 Missense Mutations in DYT6 Dystonia.
Mutations in THAP1 (THAP domain-containing apoptosis-associated protein 1) are responsible for DYT6 dystonia. Until now, more than eighty different mutations in THAP1 gene have been found in patients with primary dystonia, and two third of them are missense mutations. The potential pathogeneses of these missense mutations in human are largely elusive. In the present study, we generated stable transfected human neuronal cell lines expressing wild-type or mutated THAP1 proteins found in DYT6 patients. Transcriptional profiling using microarrays revealed a set of 28 common genes dysregulated in two mutated THAP1 (S21T and F81L) overexpression cell lines suggesting a common mechanism of these mutations. ChIP-seq showed that THAP1 can bind to the promoter of one of these genes, superoxide dismutase 2 (SOD2). Overexpression of THAP1 in SK-N-AS cells resulted in increased SOD2 protein expression, whereas fibroblasts from THAP1 patients have less SOD2 expression, which indicates that SOD2 is a direct target gene of THAP1. In addition, we show that some THAP1 mutations (C54Y and F81L) decrease the protein stability which might also be responsible for altered transcription regulation due to dosage insufficiency. Taking together, the current study showed different potential pathogenic mechanisms of THAP1 mutations which lead to the same consequence of DYT6 dystonia.


A case of idiopathic granulomatous interstitial nephritis with an unusually large granuloma.
Granulomatous interstitial nephritis (GIN) is a rare disease. Contributing factors such as drugs, sarcoidosis, infections, and paraproteinemia have been reported, and when no obvious contributing factors can be identified, the disease is classified as idiopathic GIN. We managed a patient with idiopathic GIN with an unusually large granuloma. Usually, granulomas are smaller or slightly larger than glomeruli. However, our patient had an atypical granuloma, and such a large granuloma has never been reported. GIN can be treated with steroids, and our patient improved after high-dose steroid treatment.


Structural characterization of the symbiotically important low-molecular-weight succinoglycan of Sinorhizobium meliloti.
The production of succinoglycan by Sinorhizobium meliloti Rm1021 is required for successful nodule invasion by the bacterium of its host plant, alfalfa. Rm1021 produces succinoglycan, an acidic exopolysaccharide composed of an octasaccharide repeating unit modified with acetyl, succinyl, and pyruvyl moieties, in both low- and high-molecular-weight forms. Low-molecular-weight (LMW) succinoglycan, previously thought to consist of monomers, trimers, and tetramers of the repeating unit, has been reported as being capable of promoting the formation of nitrogen-fixing nodules by succinoglycan-deficient derivatives of strain Rm1021. We have determined that the three size classes of LMW succinoglycan species are in fact monomers, dimers, and trimers of the repeating unit and that the trimer is the species active in promoting nodule invasion. A detailed structural analysis of the components of LMW succinoglycan by using various chromatographic techniques, along with nuclear magnetic resonance analyses, has revealed that there is considerable heterogeneity within the LMW succinoglycan oligomers in terms of noncarbohydrate substitutions, and we have determined the structural basis of this heterogeneity.


Photocatalytic synthesis of urea from in situ generated ammonia and carbon dioxide.
TiO(2) and Fe-titanate (different wt%) supported on zeolite were prepared by sol-gel and solid-state dispersion methods. The photocatalysts prepared were characterized by X-ray diffraction, scanning electron microscopy and ultraviolet (UV)-visible diffuse reflectance spectroscopy techniques. Photocatalytic reduction of nitrate in water and isopropanol/oxalic acid as hole scavengers are investigated in a batch reactor under UV illumination. The yield of urea increased notably when the catalysts were supported on zeolite. The Fe-titanate supported catalyst promotes the charge separation that contributes to an increase in selective formation of urea. The product formation is because of the high adsorption of in situ generated CO(2) and NH(3) over shape-selective property of the zeolite in the composite photocatalyst. The maximum yield of urea is found to be 18 ppm while 1% isopropanol containing solution over 10 wt% Fe-titanate/HZSM-5 photocatalyst was used.


24-Hour urinary glucose excretion in assessment of control in juvenile diabetes mellitus.
24-Hour urinary glucose excretion was measured in 43 juvenile diabetics during treatment as outpatients. In 20 children studied twice over 1-3 months there was good correlation between glucose excretion on each occasion. Subdivision of the collections into the periods 08 therefore 00-20 therefore 00 and 20 therefore 00-08 therefore 00 hours gave slightly less consistent results with correlation coefficients of 0 therefore 83 and 0 therefore 80, respectively, between the results of the repeat tests. In 37 prepubertal children, 24-hour glucose concentration and height velocity over the previous year were compared, and a highly significant negative correlation found. 10 of the 12 children with glucose excretion greater than 40 g/d had height velocities more than 1 SD below the mean for age, while only 2 of the 25 subjects excreting less than 40 g/d had height velocities more than 1 SD below the mean. The results indicate that estimation of 24-hour urine glucose excretion can be a useful index for monitoring treatment and that subdivision of the total collection may be of value in selecting the most suitable insulin regimen for the patient.


Use of polymeric CXCR4 inhibitors as siRNA delivery vehicles for the treatment of acute myeloid leukemia.
Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and is associated with poor long-term survival often owing to relapse. Current treatments for AML are associated with considerable toxicity and are frequently not effective after relapse. Thus, it is important to develop novel therapeutic strategies. Short interfering RNA (siRNA)-based therapeutics targeting key oncogenes have been proposed as treatments for AML. We recently developed novel siRNA delivery polycations (PCX) based on AMD3100 (plerixafor), an FDA-approved inhibitor of the CXC chemokine receptor 4 (CXCR4). Inhibitors of CXCR4 have been shown to sensitize leukemia cells to chemotherapy. Therefore, PCX has the potential to target leukemia cells via two mechanisms: inhibition of CXCR4 and delivery of siRNAs against critical genes. In this report, we show that PCX exerts a cytotoxic effect on leukemia cells more effectively than other CXCR4 inhibitors, including AMD3100. In addition, we show that PCX can deliver siRNAs against the transcription factor RUNX1 to mouse and human leukemia cells. Overall, our study provides the first evidence that dual-function PCX/siRNA nanoparticles can simultaneously inhibit CXCR4 and deliver siRNAs, targeting key oncogenes in leukemia cells and that PCX/siRNA has clinical potential for the treatment of AML.


Social Security Disability Insurance Enrollment and Health Care Employment.
To examine the relationship between Social Security Disability Insurance (SSDI) enrollment and health care employment. State-year level data from government and other publicly available sources for all states (2000-2014). Population-weighted linear regression analyses model associations between each health care employment measure and each SSDI enrollment measure (i.e., SSDI overall, physical, or mental health enrollment rates), controlling for factors associated with health care employment, state fixed effects, and secular time trends. Data are gathered from publicly available sources. A one standard deviation increase in SSDI enrollment per 100,000 population is associated with a statistically significant 2.6 and 4.5 percent increase in the mean employment rate per 100,000 population for health care practitioner and technical occupations and health care support occupations, respectively. The size of this relationship varies by the type of disabling condition for SSDI enrollment (physical versus mental health). Social Security Disability Insurance enrollment is significantly associated with health care employment at the state level. Quantifying the magnitude of this relationship is important given high SSDI enrollment rates as well as evolving policy and demographic shifts related to the SSDI program.


Multicenter phase II study of bendamustine for relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma.
Bendamustine is a unique cytotoxic agent that has demonstrated efficacy in the treatment of indolent B-cell non-Hodgkin lymphomas (B-NHLs). In this multicenter phase II trial, the efficacy and safety of bendamustine were evaluated in Japanese patients with relapsed or refractory indolent B-NHL or mantle-cell lymphoma (MCL). Patients received bendamustine (120 mg/m(2) ) on days 1-2 of a 21-day cycle, for up to six cycles. The primary endpoint was the overall response rate (ORR) as assessed by an extramural committee according to International Workshop Response Criteria (IWRC). Secondary endpoints included complete response (CR) rate, ORR according to Revised Response Criteria (revised RC), progression-free survival (PFS), and safety. Fifty-eight patients with indolent B-NHL and 11 with MCL were enrolled. By IWRC, bendamustine produced an ORR of 91% (95% confidence interval [CI], 82-97%; 90% and 100% in patients with indolent B-NHL and MCL, respectively), with a CR rate of 67% (95% CI, 54-78%). ORR and CR rates according to revised RC were 93% (95% CI, 84-98%) and 57% (95% CI, 44-68%), respectively. After a median follow-up of 12.6 months, median PFS had not been reached. Estimated PFS rates at 1 year were 70% and 90% among indolent B-NHL and MCL patients, respectively. Bendamustine was generally well tolerated. Reversible myelosuppression, including grade 3/4 leukopenia (65%) and neutropenia (72%), was the most clinically significant toxicity observed. Common non-hematologic toxicities included mild gastrointestinal events and fatigue. These results demonstrate the high efficacy and tolerability of single-agent bendamustine in relapsed patients with indolent B-NHL or MCL histologies.


Anoxia tolerance of the adult Australian Plague Locust (Chortoicetes terminifera).
Optimal breeding conditions for locust swarms often include heavy rainfall and flooding, exposing individuals to the risk of immersion and anoxia. We investigated anoxia tolerance in solitarious and gregarious adults of the Australian Plague Locust, Chortoicetes terminifera, by measuring the time to enter an anoxic coma after submersion in water, the time for recovery of ventilation and the ability to stand on return to air. We found a longer time to succumb in immature adults that we attribute to a larger tracheal volume. Time to succumb was also longer after autotomizing the hindlegs to reduce the energetic cost of muscular activity. Time to recover was longer in gregarious males and this developed during maturation, suggesting an increase in the cost of neural processing associated with social interactions under crowded conditions. Short-term changes in rearing conditions had effects that we interpret as stress responses, potentially mediated by octopamine.


Neuroimaging, cognitive, and neurobehavioral outcomes following carbon monoxide poisoning.
Carbon monoxide is a colorless, odorless gas produced as a byproduct of combustion. Carbon monoxide is the leading cause of poisoning injury and death worldwide. Morbidity following CO poisoning includes neurologic sequelae, neuropathologic abnormalities on brain imaging, neurobehavioral changes, and cognitive impairments. It is estimated that as high as 50% of individuals with carbon monoxide poisoning will develop neurologic, neurobehavioral, or cognitive sequelae. Carbon monoxide related cognitive impairments included impaired memory, attention, executive function, motor, visual spatial, and slow mental processing speed. Given the high rate of brain related morbidity and the fact that the majority of carbon monoxide is avoidable, awareness and prevention of carbon monoxide poisoning is warranted.


Moving the systemic evolutionary approach to cancer forward: Therapeutic implications.
We have previously presented a new Systemic Evolutionary Theory of Cancer (SETOC) based on the failure of proper endosymbiosis in eukaryotic cells. Here, we propose that the progressive uncoupling of two endosymbiotic subsystems (information and energy) inside the cell, as a consequence of long-term injuries, gives rise to alterations (i) in tissue interactions and (ii) in cell organization. In the first case, we argue that the impairment of both the coherent state and the synergy between intercellular communications underpins the onset of tissue dysplasia, that usually evolves towards cancer development. In the second case, we suggest that the rupture of endosymbiosis drives a sort of cell regression towards a protist-like entity represented by the concept of "de-emergence" postulated in our systemic evolutionary approach to carcinogenesis. This conceptual association of the cancer cell with a protist-like organism could support the development of novel cancer therapeutic approaches. To this end, we propose a paradigm shift in cancer pharmacology since: i) our knowledge of cancer pathophysiology as a complex system is insufficient, despite a vast knowledge of molecular mechanisms underlying cancer; ii) current cancer pharmacology deals only with microvariables (e.g. gene or protein targets), which do not account for the integrated pathophysiology of cancer, rather than with macrovariables (e.g. pH, membrane potential, electromagnetic fields, cell communications and so on) and mesovariables (between micro and macro), such as the interaction between various cellular components including cellular organelles. This paradigm shift should allow cancer pharmacology to move forward from molecular treatments (focusing on single targets) to modular treatments that consider cancer-related processes (i.e. inflammation, coagulation, etc.) or even to a sort of ecosystemic treatment addressing the whole functioning of the "cancer ecosystem". Examples of ecosystems treatment may be natural plant derivatives that act synergistically or pulsed electromagnetic fields which can act on particular biological processes in cancer cells. In addition, we need different working theoretical models on which to base new anticancer pharmacological approaches. Finally, we examine what value our systemic evolutionary approach could add to cancer treatments, in particular in liver cancer as a paradigm for developing potential applications.


Digital multiplexed gene expression analysis using the NanoString nCounter system.
This unit presents the protocol for the NanoString nCounter Gene Expression Assay, a robust and highly reproducible method for detecting the expression of up to 800 genes in a single reaction with high sensitivity and linearity across a broad range of expression levels. The methodology serves to bridge the gap between genome-wide (microarrays) and targeted (real-time quantitative PCR) expression profiling. The nCounter assay is based on direct digital detection of mRNA molecules of interest using target-specific, color-coded probe pairs. It does not require the conversion of mRNA to cDNA by reverse transcription or the amplification of the resulting cDNA by PCR. Each target gene of interest is detected using a pair of reporter and capture probes carrying 35- to 50-base target-specific sequences. In addition, each reporter probe carries a unique color code at the 5' end that enables the molecular barcoding of the genes of interest, while the capture probes all carry a biotin label at the 3' end that provides a molecular handle for attachment of target genes to facilitate downstream digital detection. After solution-phase hybridization between target mRNA and reporter-capture probe pairs, excess probes are removed and the probe/target complexes are aligned and immobilized in the nCounter cartridge, which is then placed in a digital analyzer for image acquisition and data processing. Hundreds of thousands of color codes designating mRNA targets of interest are directly imaged on the surface of the cartridge. The expression level of a gene is measured by counting the number of times the color-coded barcode for that gene is detected, and the barcode counts are then tabulated.


Membrane flow through the Golgi apparatus: specific disassembly of the cis-Golgi network by ATP depletion.
Incubation of NRK cells for 30 to 45 minutes with 50 mM 2-deoxy-D-glucose (DOG) in glucose and pyruvate-free medium results in depletion of the cellular ATP pool and in specific disassembly of the cis-Golgi network (CGN), with the stack of Golgi cisternae (SGC) and the trans-Golgi network (TGN) remaining intact and sensitive to BFA. The disassembly of the CGN is mediated by long tubular structures extending outwards from the Golgi complex and involves microtubules. Upon removal of DOG and addition of glucose and pyruvate to the culture medium, the morphology of the CGN is slowly reestablished. Reconstruction of the CGN involves COPI/COPII-positive vesicles that resume the transport of proteins and in particular of CGN membrane proteins out of the ER. Exit of CGN membrane proteins from the ER is insensitive to BFA. In cells pretreated with nocodazole, the CGN membrane proteins are transported to the vicinity of the SGC fragments dispersed throughout the cytoplasm. Ultrastructural studies of cells engaged in the reconstruction of the CGN revealed that the CGN cisterna emerge as tubular structures extending from 0.2-0.3 microm uncoated vesicles prior to their organization on the cis-side of the SGC.


[The contraceptive efficacy and mechanism of action of combinations of ethinyl estradiol and norethisterone acetate].
The purpose of the study was to establish the optimal combinations of ethynilestradiol and norethysterone acetate exhibiting a high contraceptive activity. It was shown that the ratio of 1:20 (ethynilestradiol 0.04 mg/kg and norethysterone acetate 0.8 mg/kg) is characterized by a high contraceptive efficacy. The inhibitory effect on the incretion of lutropin and follitropin leading to the change of the process of oogenesis and gravidary reorganization of the endometrium underlies probably the mechanism of action.


The composition of glyphosate-tolerant soybean seeds is equivalent to that of conventional soybeans.
One important aspect of the safety assessment of genetically engineered crops destined for food and feed uses is the characterization of the consumed portion of the crop. One crop currently under development, glyphosate-tolerant soybeans (GTS), was modified by the addition of a glyphosate-tolerance gene to a commercial soybean cultivar. The composition of seeds and selected processing fractions from two GTS lines, designated 40-3-2 and 61-67-1, was compared with that of the parental soybean cultivar, A5403. Nutrients measured in the soybean seeds included macronutrients by proximate analyses (protein, fat, fiber, ash, carbohydrates), amino acids and fatty acids. Antinutrients measured in either the seed or toasted meal were trypsin inhibitor, lectins, isoflavones, stachyose, raffinose and phytate. Proximate analyses were also performed on batches of defatted toasted meal, defatted nontoasted meal, protein isolate, and protein concentrate prepared from GTS and control soybean seeds. In addition, refined, bleached, deodorized oil was made, along with crude soybean lecithin, from GTS and control soybeans. The analytical results demonstrated the GTS lines are equivalent to the parental, conventional soybean cultivar.


Nordic Walking Can Be Incorporated in the Exercise Prescription to Increase Aerobic Capacity, Strength, and Quality of Life for Elderly: A Systematic Review and Meta-Analysis.
The aim of this systematic review and meta-analysis was to summarize and analyze the effects of Nordic Walking on physical fitness, body composition, and quality of life in the elderly. Keyword "Nordic Walking" associated with "elderly" AND/OR "aging" AND/OR "old subjects" AND/OR "aged" AND/OR "older adults" were used in the online database MEDLINE, Embase, PubMed, Scopus, PsycINFO, and SPORTDiscus. Only studies written in English language and published in peer-reviewed journals were considered. A meta-analysis was performed and effect sizes calculated. Fifteen studies were identified; age of participants ranged from 60 to 92 years old. Comparing with a sedentary group, effect sizes showed that Nordic Walking was able to improve dynamic balance (0.30), functional balance (0.62), muscle strength of upper (0.66) and lower limbs (0.43), aerobic capacity (0.92), cardiovascular outcomes (0.23), body composition (0.30), and lipid profile (0.67). It seemed that Nordic Walking had a negative effect on static balance (-0.72). Comparing with a walking (alone) training, effect sizes showed that Nordic Walking improved the dynamic balance (0.30), flexibility of the lower body (0.47), and quality of life (0.53). Walking training was more effective in improving aerobic capacity (-0.21). Comparing Nordic Walking with resistance training, effect sizes showed that Nordic Walking improved dynamic balance (0.33), muscle strength of the lower body (0.39), aerobic capacity (0.75), flexibility of the upper body (0.41), and the quality of life (0.93). Nordic Walking can be considered as a safe and accessible form of aerobic exercise for the elderly population, able to improve cardiovascular outcomes, muscle strength, balance ability, and quality of life.


Operative and Conservative Management of Laryngeal Contact Granuloma: A Network Analysis and Systematic Review.
Laryngeal contact granuloma is a disease of benign hypertrophic granulation tissue at the medial side of vocal process. Numerous studies of conservative and surgical management have reported effectiveness, yet optimal treatment has not been standardized. We compared primary and secondary outcomes of conservative and surgical treatment using endoscopic grading, Voice Handicap Index-10 (VHI-10), maximum phonation time (MPT), and recurrence rate. We performed literature searches of MEDLINE, PubMed, and EMBASE from November 1985 to October 2017, with randomized controlled trials and case control studies of at least three months follow-up as the inclusion criteria. Outcomes included laryngoscopic findings, MPT, and VHI-10. Data regarding study design, outcome analysis, follow-up time, and disease remission were systematically collected. A total of 1069 patients were abstracted from 19 papers. With conservative treatment, 98% of patients' laryngeal granuloma resolved within three months, and 84% for the surgical group. There was a decrease in VHI-10 of 2.69 (95% credible interval (CI) -9.52 to 3.82) and 6.48 (95% CI -15.00 to 1.94) for conservative and surgical management, respectively. MPT improvement was 1.27 s (95% CI: 2.03-5.84) for conservative treatment and 5.02 s (95% CI: 0.78-8.07) for surgical. For all 19 studies, absolute recurrence risk for control, conservative, and surgical measures were respectively 4%, 16%, and 29%. Most patients treated conservatively or surgically alone responded to treatment, but conservative management was favored. VHI-10 and MPT improvement in surgical patients were noted, but only the latter was statistically significant. In regard to recurrence, conservative management had better outcome than surgical. Taken together, the results suggest that minimally symptomatic granulomas have higher response rate and lower recurrence risk when treated conservatively, while larger, symptomatic granulomas may favor surgical excision followed by medical management to reduce risk of recurrence.